Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Intravenous TKM-080301 in Subjects With Advanced Hepatocellular Carcinoma

Study design: Open label, multi-center, 3 + 3 dose-escalation study with an expansion cohort
at the maximum tolerated dose (MTD) to investigate safety, tolerability, PK, and preliminary
anti-tumor activity of TKM 080301 in subjects with HCC.

Sequential cohorts of 3 to 6 subjects will receive escalating doses of TKM 080301 according
to a pre-specified dose escalation scheme. Assessment of dose-limiting toxicities (DLTs) will
be made during Cycle 1 to determine the maximum tolerated dose (MTD). Once the MTD level is
established, approximately 20 subjects will be enrolled in an expansion cohort to further
confirm the safety and tolerability of TKM-080301 at the MTD.

Study Population: A minimum of 9 and up to approximately 18 adult male or female subjects
with histologically or cytologically confirmed metastatic or locally advanced inoperable HCC
and a life expectancy of 3 months or more are planned in the dose escalation phase.
Approximately 20 subjects are planned in the expansion cohort.

Study Treatment: TKM-080301 will be administered by intravenous (IV) infusion, once weekly
for 3 consecutive weeks followed by a 1 week rest period. This 28-day treatment period
constitutes 1 cycle.

Subjects who demonstrate clinical benefit without progression per RECIST 1.1 guidelines may
receive treatment beyond 6 cycles if the Investigator considers it is in the best interest of
the subject, and only with the approval of the Medical Monitor. Subjects would then continue
TKM 080301 therapy until withdrawal of consent, disease progression or unacceptable toxicity
occurs.

Pharmacokinetics (PK) Subjects will undergo blood sample collection for PK analysis during
cycles 1 and 2.

Study Duration: Each treatment cycle will have duration of 28 days and each subject will
typically receive up to 6 cycles of treatment. The total duration of the study is expected to
be approximately 28 months.

Key Inclusion Criteria:

- Child-Pugh class of A

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5.0 × ULN

- Total bilirubin ≤3.0 mg/dL

- Platelets ≥75,000 /mL

- International Normalized Ratio (INR) ≤1.7

- Subjects must meet the protocol-defined criteria for both hepatitis B virus (HBV) and
hepatitis C virus (HCV) status

Key Exclusion Criteria:

- History of significant cardiovascular disease will be excluded

- History of liver transplant.

- Diagnosis of fibrolamellar HCC or tumors of mixed histology.

- Subjects known to be positive for Human immunodeficiency virus (HIV) infection.

- Known central nervous system (CNS) or brain metastases.

- Poorly controlled ascites and/or requirement for therapeutic paracentesis more
frequently than once every 3 months.

- Symptomatic encephalopathy within 3 months prior to the first dose of TKM-080301
and/or requirement for medication for encephalopathy.

- Esophageal variceal bleeding within 2 weeks prior to the first dose of TKM-080301.

- Asthma or chronic obstructive pulmonary disease (COPD) requiring daily medication.

- Prior therapy with nitrosoureas or mitomycin within 6 weeks prior to the first dose of
TKM-080301.

- Prior therapy with any biologic chemotherapeutic or investigational drug within 5
half-lives or 3 weeks, whichever is longer prior to the first dose of TKM 080301.